60 YEARS OF POMC: Melanocortin receptors: evolution of ligand selectivity for melanocortin peptides

2016 ◽  
Vol 56 (4) ◽  
pp. T119-T133 ◽  
Author(s):  
Robert M Dores ◽  
Liang Liang ◽  
Perry Davis ◽  
Alexa L Thomas ◽  
Bogdana Petko
Keyword(s):  
Amino Acid Sequences ◽  
Melanocortin Receptors ◽  
Accessory Protein ◽  
Ligand Selectivity ◽  
Common Precursor ◽  
Melanocortin Peptides ◽  
Genome Duplications ◽  
Duplication Events ◽  
High Conservation ◽  
Early Radiation

The evolution of the melanocortin receptors (MCRs) is linked to the evolution of adrenocorticotrophic hormone (ACTH), the melanocyte-stimulating hormones (MSHs), and their common precursor pro-opiomelanocortin (POMC). The origin of the MCRs and POMC appears to be grounded in the early radiation of the ancestral protochordates. During the genome duplications that have occurred during the evolution of the chordates, the organization plan for POMC was established, and features that have been retained include, the high conservation of the amino acid sequences of α-MSH and ACTH, and the presence of the HFRW MCR activation motif in all of the melanocortin peptides (i.e. ACTH, α-MSH, β-MSH, γ-MSH, and δ-MSH). For the MCRs, the chordate genome duplication events resulted in the proliferation of paralogous receptor genes, and a divergence in ligand selectivity. While most gnathostome MCRs can be activated by either ACTH or the MSHs, teleost and tetrapod MC2R orthologs can only be activated by ACTH. The appearance of the accessory protein, MRAP1, paralleled the emergence of teleost and tetrapods MC2R ligand selectivity, and the dependence of these orthologs on MRAP1 for trafficking to the plasma membrane. The accessory protein, MRAP2, does not affect MC2R ligand selectivity, but does influence the functionality of MC4R orthologs. In this regard, the roles that these accessory proteins may play in the physiology of the five MCRs (i.e. MC1R, MC2R, MC3R, MC4R, and MC5R) are discussed.

Functional characterization of the modified melanocortin peptides responsible for ligand selectivity at the human melanocortin receptors

Peptides ◽  
2006 ◽  
Vol 27 (11) ◽  
pp. 2836-2845 ◽  
Author(s):  
Min Chen ◽  
Keith E. Georgeson ◽  
Carroll M. Harmon ◽  
Carrie Haskell-Luevano ◽  
Yingkui Yang
Keyword(s):  
Functional Characterization ◽  
Melanocortin Receptors ◽  
Ligand Selectivity ◽  
Melanocortin Peptides

scholarly journals Molecular Phylogenetic Analysis of the AIG Family in Vertebrates

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1190
Author(s):  
Yuqi Huang ◽  
Minghao Sun ◽  
Lenan Zhuang ◽  
Jin He
Keyword(s):  
Phylogenetic Analysis ◽  
Gene Family ◽  
Functional Characterization ◽  
Vertebrate Evolution ◽  
Molecular Phylogenetic Analysis ◽  
Whole Genome Duplications ◽  
Genome Duplications ◽  
Molecular Phylogenetic ◽  
Duplication Events ◽  
Inducible Genes

Androgen-inducible genes (AIGs), which can be regulated by androgen level, constitute a group of genes characterized by the presence of the AIG/FAR-17a domain in its protein sequence. Previous studies on AIGs demonstrated that one member of the gene family, AIG1, is involved in many biological processes in cancer cell lines and that ADTRP is associated with cardiovascular diseases. It has been shown that the numbers of AIG paralogs in humans, mice, and zebrafish are 2, 2, and 3, respectively, indicating possible gene duplication events during vertebrate evolution. Therefore, classifying subgroups of AIGs and identifying the homologs of each AIG member are important to characterize this novel gene family further. In this study, vertebrate AIGs were phylogenetically grouped into three major clades, ADTRP, AIG1, and AIG-L, with AIG-L also evident in an outgroup consisting of invertebrsate species. In this case, AIG-L, as the ancestral AIG, gave rise to ADTRP and AIG1 after two rounds of whole-genome duplications during vertebrate evolution. Then, the AIG family, which was exposed to purifying forces during evolution, lost or gained some of its members in some species. For example, in eutherians, Neognathae, and Percomorphaceae, AIG-L was lost; in contrast, Salmonidae and Cyprinidae acquired additional AIG copies. In conclusion, this study provides a comprehensive molecular phylogenetic analysis of vertebrate AIGs, which can be employed for future functional characterization of AIGs.

The melanocortin system

2003 ◽  
Vol 284 (3) ◽  
pp. E468-E474 ◽  
Author(s):  
Ira Gantz ◽  
Tung M. Fong
Keyword(s):  
Sexual Function ◽  
Energy Homeostasis ◽  
Melanocortin Receptors ◽  
Experimental Basis ◽  
Melanocortin System ◽  
Genetic Studies ◽  
Melanocortin Peptides ◽  
Selective Agonists ◽  
Made In

The melanocortin system consists of melanocortin peptides derived from the proopiomelanocortin gene, five melanocortin receptors, two endogenous antagonists, and two ancillary proteins. This review provides an abbreviated account of the basic biochemistry, pharmacology, and physiology of the melanocortin system and highlights progress made in four areas. In particular, recent pharmacological and genetic studies have affirmed the role of melanocortins in pigmentation, inflammation, energy homeostasis, and sexual function. Development of selective agonists and antagonists is expected to further facilitate the investigation of these complex physiological functions and provide an experimental basis for new pharmacotherapies.

Pharmacological effect of human melanocortin-2 receptor accessory protein 2 variants on hypothalamic melanocortin receptors

Endocrine ◽  
2018 ◽  
Vol 61 (1) ◽  
pp. 94-104 ◽  
Author(s):  
Jinye Liang ◽  
Lei Li ◽  
Xuanxuan Jin ◽  
Bingxin Xu ◽  
Linyu Pi ◽  
...  
Keyword(s):  
Pharmacological Effect ◽  
Melanocortin Receptors ◽  
Accessory Protein ◽  
Receptor Accessory Protein

Isolation and characterization of the pea cytochrome c oxidase Vb gene

Genome ◽  
2006 ◽  
Vol 49 (11) ◽  
pp. 1481-1489 ◽  
Author(s):  
Nakao Kubo ◽  
Shin-ichi Arimura ◽  
Nobuhiro Tsutsumi ◽  
Koh-ichi Kadowaki ◽  
Masashi Hirai
Keyword(s):  
Amino Acid ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Fluorescent Proteins ◽  
Amino Acid Sequences ◽  
Homology Search ◽  
Coding Region ◽  
Angiosperm Evolution ◽  
Isolation And Characterization ◽  
Duplication Events

Three copies of the gene that encodes cytochrome c oxidase subunit Vb were isolated from the pea (PscoxVb-1, PscoxVb-2, and PscoxVb-3). Northern Blot and reverse transcriptase-PCR analyses suggest that all 3 genes are transcribed in the pea. Each pea coxVb gene has an N-terminal extended sequence that can encode a mitochondrial targeting signal, called a presequence. The localization of green fluorescent proteins fused with the presequence strongly suggests the targeting of pea COXVb proteins to mitochondria. Each pea coxVb gene has 5 intron sites within the coding region. These are similar to Arabidopsis and rice, although the intron lengths vary greatly. A phylogenetic analysis of coxVb suggests the occurrence of gene duplication events during angiosperm evolution. In particular, 2 duplication events might have occurred in legumes, grasses, and Solanaceae. A comparison of amino acid sequences in COXVb or its counterpart shows the conservation of several amino acids within a zinc finger motif. Interestingly, a homology search analysis showed that bacterial protein COG4391 and a mitochondrial complex I 13 kDa subunit also have similar amino acid compositions around this motif. Such similarity might reflect evolutionary relationships among the 3 proteins.

A common precursor for the three subunits ofL-glutamate oxidase encoded bygoxgene fromStreptomyces platensisNTU3304

2001 ◽  
Vol 47 (3) ◽  
pp. 269-275 ◽  
Author(s):  
Chien-Yuan Chen ◽  
Wen-Tung Wu ◽  
Chang-Jen Huang ◽  
Mei-Huei Lin ◽  
Chen-Kai Chang ◽  
...  
Keyword(s):  
Amino Acid Sequences ◽  
Binding Motif ◽  
Protein Coding ◽  
Reading Frame ◽  
Streptomyces Platensis ◽  
C Terminus ◽  
Common Precursor ◽  
Glutamate Oxidase ◽  
Negative Effect ◽  
Molecular Masses

A segment of DNA containing the L-glutamate oxidase (gox) gene from Streptomyces platensis NTU3304 was cloned. The entire nucleotide sequence of the protein-coding portion consisting of 2130 bp (710 codons, including AUG and UGA) of the cloned DNA fragment was determined. The gox gene contained only one open reading frame (ORF) which coded for a 78-kDa polypeptide, the precursor of active extracellular Gox. Mature Gox is composed of three subunits, designated as α, β, and γ, with molecular masses of 39, 19, and 16 kDa, respectively. Analyses of the N-terminal amino acid sequences of the subunits revealed that the order of subunits in the precursor polypeptide encoded by the ORF, from N-terminus to C-terminus, is α–γ–β. The presence of the flavin adenine dinucleotide (FAD)-binding motif place Gox as a member of the flavoenzyme family. Furthermore, a negative effect of glucose on the biosynthesis of Gox was observed when it was used as carbon source.Key words: L-glutamate oxidase, gox gene, signal peptide, DNA sequence, flavoenzyme, pIJ702 vector.

scholarly journals MOLECULAR EVOLUTION OF GPCRS: Melanocortin/melanocortin receptors

2014 ◽  
Vol 52 (3) ◽  
pp. T29-T42 ◽  
Author(s):  
Robert M Dores ◽  
Richard L Londraville ◽  
Jeremy Prokop ◽  
Perry Davis ◽  
Nathan Dewey ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Focal Point ◽  
Cartilaginous Fish ◽  
G Protein Coupled Receptors ◽  
Melanocortin Receptors ◽  
Accessory Proteins ◽  
Melanocortin 1 Receptor ◽  
Ligand Selectivity ◽  
G Protein Coupled ◽  
Receptor Accessory Protein

The melanocortin receptors (MCRs) are a family of G protein-coupled receptors that are activated by melanocortin ligands derived from the proprotein, proopiomelanocortin (POMC). During the radiation of the gnathostomes, the five receptors have become functionally segregated (i.e. melanocortin 1 receptor (MC1R), pigmentation regulation; MC2R, glucocorticoid synthesis; MC3R and MC4R, energy homeostasis; and MC5R, exocrine gland physiology). A focus of this review is the role that ligand selectivity plays in the hypothalamus/pituitary/adrenal–interrenal (HPA–I) axis of teleosts and tetrapods as a result of the exclusive ligand selectivity of MC2R for the ligand ACTH. A second focal point of this review is the roles that the accessory proteins melanocortin 2 receptor accessory protein 1 (MRAP1) and MRAP2 are playing in, respectively, the HPA–I axis (MC2R) and the regulation of energy homeostasis by neurons in the hypothalamus (MC4R) of teleosts and tetrapods. In addition, observations are presented on trends in the ligand selectivity parameters of cartilaginous fish, teleost, and tetrapod MC1R, MC3R, MC4R, and MC5R paralogs, and the modeling of the HFRW motif of ACTH(1–24) when compared with α-MSH. The radiation of the MCRs during the evolution of the gnathostomes provides examples of how the physiology of endocrine and neuronal circuits can be shaped by ligand selectivity, the intersession of reverse agonists (agouti-related peptides (AGRPs)), and interactions with accessory proteins (MRAPs).

scholarly journals Selective Gene Loss of Visual and Olfactory Guanylyl Cyclase Genes Following the Two Rounds of Vertebrate-Specific Whole-Genome Duplications

2020 ◽  
Vol 12 (11) ◽  
pp. 2153-2167
Author(s):  
Matthias Gesemann ◽  
Stephan C F Neuhauss
Keyword(s):  
Visual Information ◽  
Bright Light ◽  
Feedback Regulation ◽  
Cell Types ◽  
Whole Genome ◽  
Whole Genome Duplications ◽  
Intracellular Signals ◽  
Genome Duplications ◽  
Duplication Events ◽  
Specific Species

Abstract Photoreceptors convey visual information and come in two flavors; dim-light and bright-light dedicated rod and cones. Both cell types feature highly specialized phototransduction cascades that convert photonic energy into intracellular signals. Although a substantial amount of phototransduction gene ohnologs are expressed either in rods or cones, visual guanylyl cyclases (GCs) involved in the calcium (Ca2+) dependent feedback regulation of phototransduction are neither rod nor cone specific. The co-existence of visual GCs in both photoreceptor types suggests that specialization of these ohnologs occurred despite their overlapping expression. Here, we analyze gene retention and inactivation patterns of vertebrate visual and closely related olfactory GCs following two rounds (2R) of vertebrate-specific whole-genome duplication events (2R WGD). Although eutherians generally use two visual and one olfactory GC, independent inactivation occurred in some lineages. Sauropsids (birds, lizards, snakes, turtles, and crocodiles) generally have only one visual GC (GC-E). Additionally, turtles (testodes) also lost the olfactory GC (GC-D). Pseudogenization in mammals occurred in specific species/families likely according to functional needs (i.e., many species with reduced vision only have GC-E). Likewise, some species not relying on scent marks lack GC-D, the olfactory GC enzyme. Interestingly, in the case of fish, no species can be found with fewer than three (two visual and one olfactory) genes and the teleost-specific 3R WGD can increase this number to up to five. This suggests that vision in fish now requires at least two visual GCs.

scholarly journals microRNAs as Indicators into the Causes and Consequences of Whole Genome Duplication Events

2021 ◽  
Author(s):  
Kevin J Peterson ◽  
Alan Beavan ◽  
Peter Chabot ◽  
Mark L McPeek ◽  
Davide Pisani ◽  
...  
Keyword(s):  
Molecular Evolution ◽  
Alternative Hypothesis ◽  
Causal Mechanism ◽  
Whole Genome ◽  
Mrna Targets ◽  
Whole Genome Duplications ◽  
Regulatory Circuits ◽  
Genome Duplications ◽  
Duplication Events ◽  
Mirna Seed

Whole genome duplications (WGDs) have long been considered the causal mechanism underlying the dramatic increase in vertebrate morphological complexity relative to invertebrates. This is due to the retention and neo-functionalization of paralogues generated during these events, evolving new regulatory circuits, and ultimately morphological novelty. Nonetheless, an alternative hypothesis suggests that behind the retention of most paralogues is not neo-functionalization, but instead the degree of the inter-connectivity of the intended gene product, as well as the mode of the WGD itself. Here, we explore both the causes and consequences of WGD by examining the distribution, expression, and molecular evolution of microRNAs (miRNAs) in both gnathostome vertebrates as well as chelicerate arthropods. We find that although the number of miRNA paralogues tracks the number of WGDs experienced within the lineage, few of these paralogues experienced changes to the seed sequence, and thus are functionally equivalent relative to their mRNA targets. Nonetheless, the paralogues generated by the gnathostome 2R allotetraploidization event are retained in higher numbers on one sub-genome relative the second, with the miRNAs found on the preferred set of paralogons showing both higher expression of mature miRNA transcripts and slower molecular evolution of the precursor miRNA sequences. Importantly, WGDs do not result in the creation of miRNA novelty, nor do WGDs correlate to increases in complexity. Instead, it is the number of miRNA seed sequences in the genome itself that not only better correlate to instances in complexification, but also mechanistically explain why complexity increases when new miRNA families are established.

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